Mini-Dose Heparin

Stanford Wessler

doi:10.1055/s-0038-1651464

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1975; 34(03): 718-726
DOI: 10.1055/s-0038-1651464

Original Article

Schattauer GmbH

Mini-Dose Heparin^[*]

Authors

Stanford Wessler

¹Department of Medicine, New York University School of Medicine, New York, N.Y., USA

Abstract

Summary

Mini-dose heparin has demonstrated a significant decrease in postoperative deep venous thrombosis as manifested by ¹²⁵I fibrinogen venous limb scans. Whether a similar benefit in lethal pulmonary emboli can be demonstrated is currently under active investigation in England and the Continent. If this European multicenter trial yields a positive result, a safe method for the primary prevention of postoperative pulmonary emboli will have been established. Such a result would encourage evaluation of mini-dose heparin for the prophylaxis of venous thromboembolism among patients with acute myocardial infarction and perhaps for arterial thrombosis complicating coronary arterial bypass surgery.

The late Carl V. Moore, when told of the original Kakkar trial and the rationale behind it, said “well, if it doesn’t work, it ought to!” That may be the way many sympathetic investigators, myself included, feel about mini-dose heparin, but in the end everyone knows that the decisions will be based on hard data.

Full Text

References

References
1 Abildgaard U. 1968; Highly purified antithrombin 3 with heparin cofactor activity prepared by disc electrophoresis. Scandinavian Journal of Clinical and Laboratory Investigation 21: 89.
2 Ballard R. M. 1973; Low doses of subcutaneous heparin in the prevention of deep venous thrombosis after gynecological surgery. Journal of Obstetrics and Gynecology British Commonwealth 80: 469.
3 Barton P. G, Jackson C. M, and Hanahan D. J. 1967; Relationships between Factor V and activated Factor X in the generation of prothrombinase. Nature 214: 923.
4 Barton P. G, Yin E. T, and Wessler S. 1970; Reactions of activated Factor X: phosphatide mixtures in vitro and in vivo. Journal of Lipid Research 11: 87.
5 Bauer G. 1954. Proceedings of the First International Conference on Thrombosis and Embolism. B. Schwabe; Basel: 721.
6 Biggs R, Denson K. W. E, Akman N, Borrett R, and Hadden M. 1970; Antithrombin III, antifactor Xa and heparin. British Journal of Haematology 19: 283.
7 Borsodi A. D, Bradshaw R. A, Rughani I. K, and Bruce R. M. 1975. Structural and functional relationships of human antithrombin III and alpha¹-antitrypsin. In: Bradshaw R. A, and Wessler S. (eds.) Heparin: Structure, Function and Clinical Implications. Plenum Press; New York: 249.
8 Brinkhous K, Smith H. P, Warner E. D, and Seegers W. H. 1939; The inhibition of blood clotting: an unidentified substance which acts in conjunction with heparin to prevent the conversion of prothrombin into thrombin. American Journal of Physiology 125: 683.
9 Burstein M. 1955; Sur l’inactivation de la thrombin par le plasma heparine. Archives internationales de Pharmacodynamie et de Therapie 101: 285.
10 Burstein M, and Guinand A. 1956; Heparine et consommation de l’antithrombine. Archives internationales de Pharmacodynamie et de Therapie 104: 435.
11 Contejean C. 1895; Recherches sur les injections intraveineuses de peptone et leur influence sur la coagulabilite du sang chez le chien. Archives of Physiology and Normal Pathology 7: 45.
12 DeTakats G. 1950; Anticoagulants in surgery. Journal of the American Medical Association 142: 527.
13 Gallus A. S, Hirsh J, Tuttle R. J, Treibilcock R, O’Brien S. E, Carroll J. J, Minden J. H, and Hudechi S. M. 1973; Small subcutaneous doses of heparin in prevention of venous thrombosis. New England Journal of Medicine 288: 545.
14 Gerendas M. 1960; Thrombin inactivation as an enzymatic process. Thrombosis et Diathesis Haemorrhagica 4: 56.
15 Gitel S. 1975. Evidence of a catalytic role of heparin in anticoagulation reactions. In: Bradshaw R. A, and Wessler S. (eds.) Heparin; Structure, Function and Clinical Implications. Plenum Press; New York: 243
16 Gordon-Smith I. C, Grundy D. J, LeQuesne L. P, NewCombe J. F, and Bramble F. J. 1972; Controlled trial of two regimens of subcutaneous heparin in prevention of postoperative deep-vein thrombosis. Lancet 1: 1133.
17 Grottum K. A, Nordøy A, and Hellem A. 1973; Blood platelet uptake of lipid and effects on platelet functions. Thrombosis et Diathesis Haemorrhagica 29: 701.
18 Hanahan D. J, and Papahadjopulos D. 1964. In: Koller F. (ed.) Genetics and the Interaction of Blood Clotting Factors. F. K. Schattauer-Verlag; Stuttgart: 71.
19 Howell W. H. 1916; The Coagulation of blood. Harvey Lecture 2: 272.
20 Hume H, Sevitt S, and Thomas D. P. 1970. Venous Thrombosis and Pulmonary Embolism. Cambridge, Massachusetts: Harvard University Press; 4.
21 Kakkar V. V, Field E. S, Nicolaides A. N, Flute P. T, Wessler S, and Yin E. T. 1971; Prevention of postoperative deep vein thrombosis – prophylactic effects of low doses of heparin. Lancet 2: 699.
22 Kakkar V. V, Corrigan T, Spindler J, Fossard D. P, Flute P. T, Crellin R. Q, Wessler S, and Yin E. T. 1972; The efficacy of low doses of heparin in the prevention of deep vein thrombosis following major surgery – a doubleblind, randomized trial. Lancet 2: 101.
23 Kakkar V. V. 1973; Low doses of heparin in the prevention of deep veinous thrombosis. Bulletin Swiss Academy of Medical Science 29: 235.
24 Lenggenhager K. 1957; Genese und Prophylaxis der postoperativen Fernthrombose. Helvetica Chirurgica Acta 24: 316.
25 MacIntyre J. M. C, Vasilescu C, Jones D. R. B, Ruckley C. V. et al. 1974; Heparin versus dextran in the prevention of deep-vein thrombosis. Lancet 2: 118.
26 Marciniak E, and Tsukamura S. 1972; Two progressive inhibitors of Factor Xa in human blood. British Journal of Haematology 22: 341.
27 Markwardt F, and Walsmann P. 1959; The reaction between hirudin and thrombin. Journal of Physiology and Chemistry 317: 64.
28 McNicol G. P. 1974; Conventional uses of heparin. Thrombosis et Diathesis Haemorrhagica 33: 97.
29 Monkhouse F. D, France E. S, and Seegers W. H. 1955; Studies on antithrombin and heparin cofactor activities of fraction absorbed from plasma by aluminum hydroxide. Circulation Research 3: 397.
30 Monkhouse F. C, and Milojevic S. 1968; Studies on the relation between plasma antithrombin and heparin-cofactor. Canadian Journal of Physiology and Pharmacology 45: 347.
31 Morawitz P. 1905; Die Chemie der Blutgerinnung. Ergebnisse der Physiologie, biologischen Chemie und experimentellen Pharmakologie 4: 307.
32 Negus D, Pinto D. J, and Slack W. W. 1971; Effect of small doses of heparin on platelet adhesiveness and lipoproteinlipase activity before and after surgery. Lancet 1: 1202.
33 Nicolaides A. N, Dupont P. A, Desai S, Lewis J. D, Douglas J. N, Dodsworth H, FouPviDES G, Luck R. J, and Jamison C. W. 1972; Small doses of subcutaneous sodium heparin in preventing deep venous thrombosis after major surgery. Lancet 2: 890.
34 Quick A. J. 1938; Normal antithrombin of blood and its relation to heparin. American Journal of Physiology 123: 712.
35 Rosenberg R, and Damus P. S. 1973; The purification and mechanism of action of human antithrombin-heparin cofactor. Journal of Biological Chemistry 248: 6490.
36 Seegers W. H, Warner E. D, Brinkhous K. M, and Smith H. P. 1942; Heparin and antithrombotic activity of plasma. Science 96: 300.
37 Seegers W. H, and Marciniak E. 1962; Inhibition of autoprothrombin C activity with plasma. Nature 193: 1188.
38 Seegers W. H, Cole E. R, Harmison C. R, and Monkhouse F. D. 1964; Neutralization of autoprothrombin C activity with antithrombin. Canadian Journal of Biochemistry 42: 359.
39 Seegers W. H. 1968; Antithrombin: a proteinase inhibitor. Annals of the New York Academy of Science 146: 593.
40 Sharnoff J. G. 1966; Results in the prophylaxis of postoperative thromboembolism. Surgery, Gynecology and Obstetrics 123: 303.
41 Sharnoff J. G, and Kim E. S. 1958; Evaluation of pulmonary megakaryocytes. Archives of Surgery 66: 176.
42 Stormorken H. 1969; The platelet release reaction. Its general aspects and relation to phagocytosis/pinocytosis. Scandinavian Journal of Clinical and Laboratory Investigation Supplement 107: 115.
43 Vital Statistics of the United States. 1969 Volume II – Mortality Part A. U.S. Department of Health, Education and Welfare, Public Health Service, Health Resources Administration, National Center for Health Statistics, pp. 1-92.
44 Waugh D. F, and Fitzgerald M. A. 1956; Quantitative aspects of antithrombin and heparin in plasma. American Journal of Physiology 184: 627.
45 Wessler S, Yin E. T, Gaston L. W, and Nicol I. 1967; A distinction between the role of precursor and activated forms of clotting factors in the genesis of stasis thrombi. Thrombosis et Diathesis Haemorrhagica 18: 12.
46 Wessler S, and Yin E. T. 1968; The experimental hypercoagulable state induced by Factor X : a comparison of the non-activated and activated forms. Journal of Laboratory and Clinical Medicine 72: 256.
47 Wessler S, and Yin E. T. 1969. On the mechanism of thrombosis. In: Brown E, and Moore C.V. (eds.) Progress in Hematology, vol. III. Grune and Stratton; New York,: 201.
48 Wessler S, and Yin E. T. 1973; The theory and practice of mini-dose heparin: a status report. Circulation 47: 671.
49 Wessler S, Kleiger R. E, Cornfield J, and Teitelbaum S. L. 1974; Coumarin therapy in acute myocardial infarction. A Hobson’s choice. Archives of Internal Medicine 134: 774.
50 Williams H. T. 1971; Prevention of postoperative deep-vein thrombosis with perioperative subcutaneous heparin. Lancet 2: 950.
51 Yin E. T, and Wessler S. 1968; Bovine thrombin and activated Factor X: separation and purification. Journal of Biological Chemistry 243: 112.
52 Yin E. T, and Wessler S. 1968; Investigation of the apparent thrombogenicity of thrombin. Thrombosis et Diathesis Haemorrhagica 20: 465.
53 Yin E. T, and Wessler S. 1969; Evidence for a naturally occurring plasma inhibitor of activated Factor X : its isolation and partial purification. Thrombosis et Diathesis Haemorrhagica 21: 398.
54 Yin E. T, and Wessler S. 1970; Heparin-accelerated inhibition of activated Factor X by its natural inhibitor. Biochimica et Biophysica Acta 201: 387.
55 Yin E. T, Wessler S, and Stoll P. J. 1971; Babbit plasma inhibitor of the activated species of blood coagulation Factor X: purification and some properties. Journal of Biological Chemistry 246: 3694.
56 Yin E. T, Wessler S, and Stoll P. J. 1971; Biological properties of the naturally occurring plasma inhibitor to activated Factor X. Journal of Biological Chemistry 246: 3703.
57 Yin E. T, Wessler S, and Stoll P. J. 1971; Identity of plasma activated Factor X inhibitor with antithrombin III and heparin cofactor. Journal of Biological Chemistry 246: 3712.
58 Yin E. T, Eisenkramer L, and Butler J. V. 1975. Heparin interaction with activated Factor X and its inhibitor. In: Bradshaw B. A, and Wessler S. (eds.) Heparin: Structure, Function and Clinical Implications. Plenum Press; New York: 239.

Mini-Dose Heparin[*]

Authors

Mini-Dose Heparin^[*]